β-selective C-arylation of silyl protected 1,6-anhydroglucose with arylalanes: the synthesis of SGLT2 inhibitors.

Area of Science:

• Organic Chemistry
• Carbohydrate Chemistry
• Medicinal Chemistry

Background:

• Beta-C-arylglucosides are important pharmaceutical building blocks.
• Developing efficient stereoselective synthetic routes is crucial for drug development.

Purpose of the Study:

• To develop a novel stereoselective arylation method for hydroxy-protected 1,6-anhydro-β-d-glucose.
• To synthesize β-C-arylglucosides with high stereoselectivity.
• To demonstrate the utility of this method in synthesizing canagliflozin.

Main Methods:

• Stereoselective arylation of protected 1,6-anhydro-β-d-glucose using modified arylalanes (Ar2AlX).
• Modification of triarylalanes with Brønsted acids or AlCl3 to enhance reactivity.
• In situ hydroxyl group protection using organoaluminum reagents.

Main Results:

• Successful synthesis of β-C-arylglucosides with high stereoselectivity.
• Demonstrated enhanced reactivity of modified arylating agents.
• Efficient synthesis of the SGLT2 inhibitor canagliflozin was achieved.

Conclusions:

• The developed method provides an efficient and stereoselective route to β-C-arylglucosides.
• Modified arylalanes offer versatile and reactive arylating agents.
• This methodology is valuable for the synthesis of complex pharmaceutical compounds like canagliflozin.